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[A. Biochemistry/Molecular Biology] A-39



             Inotodiol Protect Human Dermal Fibroblast Against Oxidative


               Stress-induced Aging by Regulating NADPH oxidase 5 and


                                                       Erk1/2




                              #
                                                 #
           Seung Hoon Lee¹ , Gun-Woo Won¹ , Seung-Hyeon Choi¹, Mi-Yoon Kim¹, Cheong-Hae Oh¹,
                                             Jong-Tae Park²,³*, Jong-Il Park¹*

          ¹Department of Biochemistry, Research Institute for Medical Science, Chungnam National University School of

           Medicine, Daejeon 35015, Korea, ²Department of Food Science and Technolo, Chungnam National University,
                Daejeon 35015, Korea, ³CARBOEXPERT Inc, Chungnam National University, Daejeon 34134, Korea




        Oxidative  damage  is  one  of  the  major  causes  of  human  skin  aging.  Inotodiol  is  a  lanostane  triterpenoid  that

        demonstrates antiviral, anticancer, and anti-inflammatory activity and inhibits food allergies. Previous studies have
        reported that inotodiol also has antiallergic effects. However, whether inotodiol inhibits hydrogen peroxide (H2O2)-

        induced oxidative stress in human skin is not known. Stimulation of human dermal fibroblast cells with H2O2 is
        related  to  skin  aging  and  upregulation  of  inflammation-related  proteins,  along  with  decreased  expression  of

        mitogen-activated protein kinases (MAPKs). Inotodiol  effectively decreased nuclear  factor kappa-light-chain-
        enhancer of activated B cells (NF-κB), as well as nitric oxide (NO), reactive oxygen species (ROS), cyclooxygenase-2

        (COX-2), and cytokines such as IL-1β and TNF-α. Moreover, inotodiol inhibited the expression of extracellular-signal-
        regulated kinases 1 and 2 (ERK1/2), which are components of the MAPK signaling pathway. Furthermore, inotodiol

        also suppressed NOX5 expression. Based on our results, inotodiol protects human dermal fibroblast by preventing
        ERK1/2, NF-κB and NOX5 activation and attenuates the expression of inflammation genes. Inotodiol may therefore

        be considered a potential candidate for developing natural antiaging products, which protects human skin from
        ROS-induced injury by inhibiting the ERK1/2 and NOX5 signaling pathway.
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